PRKDC_XENLA
ID PRKDC_XENLA Reviewed; 4146 AA.
AC Q9DEI1; O57402;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=DNA-dependent protein kinase catalytic subunit;
DE Short=DNA-PK catalytic subunit;
DE Short=DNA-PKcs;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P78527};
GN Name=prkdc;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=J; TISSUE=Spleen;
RX PubMed=11003390; DOI=10.1007/s002510000227;
RA Fujimori A., Araki R., Fukumura R., Ohhata T., Takahashi H., Kawahara A.,
RA Tatsumi K., Abe M.;
RT "Identification of four highly conserved regions in DNA-PKcs.";
RL Immunogenetics 51:965-973(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3507-4146.
RC TISSUE=Liver;
RX PubMed=9426255; DOI=10.1016/s0378-1119(97)00498-8;
RA Labhart P.;
RT "mRNA encoding the catalytic subunit of DNA-dependent protein kinase is
RT widely expressed in Xenopus cells.";
RL Gene 203:235-240(1997).
CC -!- FUNCTION: Serine/threonine-protein kinase that acts as a molecular
CC sensor for DNA damage. Involved in DNA nonhomologous end joining (NHEJ)
CC required for double-strand break (DSB) repair and V(D)J recombination.
CC Must be bound to DNA to express its catalytic properties. Promotes
CC processing of hairpin DNA structures in V(D)J recombination by
CC activation of the hairpin endonuclease artemis (DCLRE1C). Recruited by
CC XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align
CC broken ends of DNA, thereby preventing their degradation, (2) and
CC sequester the DSB for repair by NHEJ. Act as a scaffold protein to aid
CC the localization of DNA repair proteins to the site of damage. The
CC assembly of the DNA-PK complex at DNA ends is also required for the
CC NHEJ ligation step. Found at the ends of chromosomes, suggesting a
CC further role in the maintenance of telomeric stability and the
CC prevention of chromosomal end fusion. As part of the DNA-PK complex,
CC involved in the early steps of ribosome assembly by promoting the
CC processing of precursor rRNA into mature 18S rRNA in the small-subunit
CC processome (By similarity). Recognizes the substrate consensus sequence
CC [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX, thereby
CC regulating DNA damage response mechanism (By similarity).
CC {ECO:0000250|UniProtKB:P78527, ECO:0000250|UniProtKB:P97313}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:P78527};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P78527};
CC -!- SUBUNIT: DNA-PK is a heterotrimer of prkdc and the Ku dimer (composed
CC of xrcc6/Ku70 and xrcc5/Ku86). Component of the core long-range non-
CC homologous end joining (NHEJ) complex (also named DNA-PK complex)
CC composed of prkdc, lig4, xrcc4, xrcc6/ku70, xrcc5/ku86 and nhej1/xlf.
CC Additional component of the NHEJ complex includes paxx. Following
CC autophosphorylation, prkdc dissociates from DNA.
CC {ECO:0000250|UniProtKB:P78527}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P78527}. Nucleus,
CC nucleolus {ECO:0000250|UniProtKB:P78527}.
CC -!- PTM: Autophosphorylated at two clusters, the T2609 cluster and the
CC S2056 cluster. Autophosphorylated on Ser-2075, Thr-2631, Thr-2659 and
CC Thr-2668. Ser-2075 and Thr-2668 are DNA damage-inducible
CC phosphorylation sites (inducible with ionizing radiation, IR)
CC dephosphorylated by PPP5C (By similarity). Autophosphorylation induces
CC a conformational change that leads to remodeling of the DNA-PK complex,
CC requisite for efficient end processing and DNA repair (By similarity).
CC Autophosphorylation in trans within DNA-PK complexes loaded on DNA ends
CC leads to the dissociation of PRKDC from DNA and the transition into the
CC short-range NHEJ complex (By similarity). Autophosphorylation of the
CC T2609 cluster is required for hematopoietic development and protein
CC synthesis in erythrocytes precursors (By similarity).
CC {ECO:0000250|UniProtKB:P78527, ECO:0000250|UniProtKB:P97313}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000305}.
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DR EMBL; AB016434; BAA36690.1; -; mRNA.
DR EMBL; AF001413; AAC60340.1; -; mRNA.
DR RefSeq; NP_001079070.1; NM_001085601.1.
DR SMR; Q9DEI1; -.
DR IntAct; Q9DEI1; 1.
DR PRIDE; Q9DEI1; -.
DR GeneID; 373602; -.
DR KEGG; xla:373602; -.
DR CTD; 373602; -.
DR Xenbase; XB-GENE-866368; prkdc.L.
DR OrthoDB; 26975at2759; -.
DR Proteomes; UP000186698; Chromosome 6L.
DR Bgee; 373602; Expressed in egg cell and 19 other tissues.
DR GO; GO:0070419; C:nonhomologous end joining complex; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004677; F:DNA-dependent protein kinase activity; IEA:InterPro.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:CACAO.
DR GO; GO:0031571; P:mitotic G1 DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0042254; P:ribosome biogenesis; IEA:UniProtKB-KW.
DR CDD; cd05172; PIKKc_DNA-PK; 1.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR037706; DNA-PK_dom.
DR InterPro; IPR012582; DNAPKcs_CC3.
DR InterPro; IPR045581; DNAPKcs_CC5.
DR InterPro; IPR003152; FATC_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR003151; PIK-rel_kinase_FAT.
DR InterPro; IPR014009; PIK_FAT.
DR Pfam; PF19704; DNAPKcs_CC5; 1.
DR Pfam; PF02259; FAT; 1.
DR Pfam; PF02260; FATC; 1.
DR Pfam; PF08163; NUC194; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR SMART; SM01343; FATC; 1.
DR SMART; SM01344; NUC194; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF48371; SSF48371; 3.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51189; FAT; 1.
DR PROSITE; PS51190; FATC; 1.
DR PROSITE; PS00915; PI3_4_KINASE_1; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; DNA damage; DNA repair; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Ribosome biogenesis;
KW Serine/threonine-protein kinase; TPR repeat; Transferase.
FT CHAIN 1..4146
FT /note="DNA-dependent protein kinase catalytic subunit"
FT /id="PRO_0000225634"
FT REPEAT 308..343
FT /note="HEAT 1"
FT REPEAT 925..962
FT /note="HEAT 2"
FT REPEAT 1026..1062
FT /note="HEAT 3"
FT REPEAT 1075..1111
FT /note="HEAT 4"
FT REPEAT 1745..1778
FT /note="TPR 1"
FT REPEAT 1974..2007
FT /note="TPR 2"
FT DOMAIN 2873..3556
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT DOMAIN 3739..4071
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 4114..4146
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 3745..3751
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 3937..3945
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 3957..3982
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT MOD_RES 2075
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P78527"
FT MOD_RES 2631
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P78527"
FT MOD_RES 2634
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P78527"
FT MOD_RES 2659
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P78527"
FT MOD_RES 2668
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P78527"
FT CONFLICT 3590
FT /note="R -> H (in Ref. 2; AAC60340)"
FT /evidence="ECO:0000305"
FT CONFLICT 3664
FT /note="E -> D (in Ref. 2; AAC60340)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 4146 AA; 473505 MW; C91F8BC517C7CBF9 CRC64;
MLLAGAGGSS GDGQDGVASG PAESAAGILG RLHQLHGLLS LESGVGAEGA HSLLHNLAEE
CLVSALGSSA LDLNTSLIFS KEFGLLAFVR KSLSSDEFKD CREEALKFLY TFLEKIGSNV
QPYAMDIKTL CVIVYTKDRA AKCKIPSLEL LIKLLQLLKN SIIIEEFKIG EIFNKFYGEL
ATKSKLSDTV LEKVYELLGI LGEVQPCEMT YNSEKLFKAF LGELKAQMNS STRNPKFPVI
AGCLKGLSAL MINFTKTMEE DPRTSKEIFD YTVKAISPQV EMKRYAVPSA GLNLLALHAS
QFSSYLMDDY QSLFEVISKW CGHTNGEMKK LAFAALDSFL KQIAHLVASD AETHKNKLHF
FMEQFYEIIR KMDSSNKELS IAIRGYGLFA APCKAVNAKN VDLMYIELIQ RCKQMYLTEA
DTEEDNVYQL PNFLQSVASV ILHMDSIPEV YTPILERLLV VQIDSFPQYS LKMQSSCCKA
VLKVFLSLAG KGPVLWSLIS TVVHQGLIRV CSKPVVLAQD GKEGSEAETA AATGEVRAGK
WKVPTYKDYL DLFRNLLRCD QLKDSIFSDE IFSTVNSPLQ SLNRLLYDEL MKSILKIIEK
LDLSLQKQDT GQEDDGGINN LLINATSDPA GNLYATKPKD FTAFVNLVEF CSEILPKEHI
EYFESWVYVF GYELVLQSTR LPLISGFYKL LSVVMKNAKK SRYFEGFTSK IYKKAPEDPE
RLSCFALFAK FGKEVSSKIR QFKDELLASC LTFVLHLPHD IIMMDIKAYI PALQTAFKLG
LSCPPLADVG LNALQYWSTN IPSDILKPYY KDIIPLLDGY LTNLSSTNES LSTLDMVRIS
RSLHKGFNKQ LIQQLKRMKT LSVKEESSLT AVRNRVVRIL GSLGGQINRS LVTAASTEEM
IKRHVSWDTE KRLRFDVPFK DLKPVIYLDM FLPHITELAL STSDRQTKVA ACELLHSIVA
FMLGKATQMP DDKKTGSSPM YKIYKRTFPV LLRLACDVDK VTEQLYKPLV MSLIHWFTNN
KKFESQDTVA LLEAILTGIV DPVDSTLRDF CGQCIQEFLR WSIKQTTPDQ QAKSPVNTTS
LFKRLYSLAL HPNAFKRLGA ALAFNNIYRD FREETALVEN FVFEVLVIYM ESLALSHADE
KSLGTTQQCS DAVDHLKRII IRKAASLNKA TKRRIPRGFP QGNTVCLFDI VLWLLEQCGR
PQTECRHKAM QLFFEFVPLL PGNKPLTAWL DDQVEKEGII FLINRFEGAG HSDGMHTGIF
NIPALHDLHE PFSMHAVLQW LDMLLAALDC YNTFIGMRFL KANTVLGKNA EKSSFLKAAF
FFITSLSMEN IKAAEQCMGS KSSVFSPHEI EAYNYSKCTI IVRIMEFITM FIDICQQDSL
KILENSVFNE PMWELIAITV CDPSSIGFNT ADVEVINNLP NICIKLMKAL GNTSYRSSLE
VSLKKRVTLQ SIEELCSVDL YDPGARFNRV KLGSVLSACK QLYKAEFFNS IVPEQVGGQR
FGSKLLSVVY KGIAPTNERK SLPSLDISSK RLAEGLLELA FMFGGQCEEL VSLLLNTVIL
SVPLPGTSQR NIINFSHGGY FYTLFAETIN TELLNNLDTI VVELMKSSLE DPKMVSCVLN
GMLDQSFRQR TIRKQQGVKL VNAVLENWRR LDSWWYKDSP SESKMAVLTL LAKVLQIDSS
VCFDINHSAF AEVFKTYTSI LTDQKLGLNL KSQAIIILPF FTKLTGEKLT ELKNTLDQFV
ASNFPMKSDE FPKGTLKFNN YVDCIKKFLD ALELSQSPML LQLMTEILCR DERHFMEELF
QSSFKKVIKR SSCDTQVILL NTLHNMFKSE SLMLNGTLQS LIDRCLLTLL WNCSLDAMIS
FFTNIISLAM DTLKSRFTKV PEAAFDSQIT KKWGYYKMLE VQYSRLSKDE IYSTVNNAYH
VSSKPEGNEL TKALIKLCYD TFTENMCGET QLLEKRRQYH CAAYNCAISL ISCVFSELKF
YQGFLFTEKK EKNLLIFENL IDLQRNYTFP IEVEVPMERK KKYFAIRKEA RDASSTESDE
PSYLSSQSYM ADSSLIEEMS QFDFSTGVQS FSYSSQSKML SQSASRKKEQ ITEGKTFDDV
MEFEMDELNQ HECMAAMTGL IKHMNRSEIT PKVDEDASPQ ELPSWMKFLH VKLGNTSTPL
NIRLFIAKLI VNTEEVFRPY ARFWIGPILQ LIVSGNNGGT GIHYMVVETL VTILSWSSIA
TPNGQAKEEI LANRLLEFLM KNVFHEKRAV FRHNLEIIKT VLECWKECLS IPYRLIYEGF
SGTDPNTKDN SVGIQLLGLA LANNFSPLDP KCGIDPERYF QSLANNLGLT RFKEVYIAAA
EVIGLVLRYI VQNEKRTEAP VFDYVVKELK RHQTNNKEDK FIMCLNKVVK NFPPFADRFM
TIVLFLLPKL HGVLKTQCLE IIMHRAEDIP DLFIELKNKD FCQIMNNRDD ERQRVCLDII
YKILSKLTPA ELHEFLIPVT AFSSHSFPVC RERMYDIFMW IYDNYRDHES QNDSKSVEVF
NMAKEGLLQG LVDENTELQL IVRNFWSDET RLPSNTTERM LAILSSLYSP KIEKHYLSLA
TNLLLEMTSK SPDYIRKMFE HPLSECKFQD YTVDSSWRFR SSVLTPMFVE TQLSQSMQRS
RAQGTIEADE PIGGQLRATQ QHYQFTPTQN IGGRSSFNWL TGSSMDTLAD YSVESPESLP
SALLFVNKRN ENVRRVPLKP LGPNFGMRRL GLPGDVTDSK TKSMEDRSDI LRLRRRFLKD
REKLSLIYAR KGTAEQKREK AIKIEQKMKQ DAQITLYRNY RQGELPDIQI SYSNLIAPLQ
ALAQRDPTMA KLLFSSLFSG ILTDTASDIS VTDKLLKQFN SFLSNSLSYF PPFIACVQDM
CYQHDELLHL NPANISTSCL ASLQQPLGIL LLEKGLLHMK VPDEPPAKKM RKEKEKAEIP
PDIVRWIELA KLYRSIGDYD VLRGIFSGKI GAKSITQCAL NAEAKSDYAK AAKLYDEALT
ETFSDGDPTD AEKDFWELAS LECYNHLTEW KPLEYCSTVN IDTGKPPDLN KMWSDPFYQE
TYLPYMIRSK LKMLLGGNND QTLLTFVDEA MKVEQRKVLM ETFYSQELSL LYILQDDFDR
AKYYINNGIQ VFMQNYSSID CLLYQSRLTK LQSVQALTET QDFISFIRKP GNVSSSSLRK
LFQGWMKRYP DSKMDPMNIW DDIISNRCFF LDKIQDVAVG HPQLVDESME VDDLADGNEA
MEVDRQEDIA VMINKCRFTM KMKMVDSARK QNNFSVAMKL LKDLHRESKT NEDWSVKWIH
SYSRYSHSRS RDLTCSEQIL TALKTIPLLE ESKTEYLTKN TKACRYQNML LGDTYRIMAD
AVCKEPDCLY KIEDGKAGKV KDLSESPENV VGGLYRKSLH YFTNAVRKAT EEEQSHSTDQ
IDVRGIIKAY MTLVDFCDSH LRKVEEESAV MDRADYQNFP EIMVEKMIKA LKLNSSEARL
KFPRMLQIIE QYPSETLDLM ARENCTVPCW QFIGWISQMM AMLDKKESIA VQHIIEEIAE
NYPQALVYPF MVSGESYNFE DTVVGHKNRE YVNRIKSKLD KDNVAQDFIR ALEQLSNPPM
IFQDWWEDVS NELSKPNVNK NKIKELYKEM YTNLGNPKDH FMGAFRRRFC EKYTKDFDKA
FGPEGSKLLN IKCDGFNKTV GPLITKMKEQ QKEPGNLKEY SPWMSEFKPE FLRNELEIPG
QYSGRSKPMP EYHVKISGFD ERVSVMASIR KPKRIIVRGN DEREYPFLVK GGEDLRQDQR
IEQLFEIMNI ILSQDAACSQ RHMQLKTYQV IPMTTRIGLI EWLENTCTLK EFILNTMTED
EAKIYNSKTT NGPLYHYNAW LDKKEKVGDA RQHVTSYTRC DRTNTVASFR EREALVPKDL
LRRAFVKMST TPEAFLSLRS HFARSHALLC VSHWIVGIGD RHLSNFMINM ETGGMIGIDF
GHAFGTATQF LPVPELMPFR LTRQIVNLML PMKDSGLFDS VMVHSLRAYR SDPGLLVTTM
DVFIKEPSLD WKNLELKQMK KKGEWKKAVD VTSHNWHPQQ KIHCAKRKLD GANPCEITCE
ELRLGHESAP EYKDFIAVAR GDKKHNRRTN EPPDGLTEET QVQCLIDQAT DPNILGRVWK
GWEPWI
